Henderson-Hasselbalch Research Articles

Drug Aggregation of Sparingly-Soluble Ionizable Drugs: Molecular Dynamics Simulations of Papaverine and Prostaglandin F2α.

Aggregation in aqueous solution can have important implications on both the in vivo exposure of a drug and its pharmaceutical manufacturability. However, the drug aggregates formed can be very small and, thus, difficult to interrogate experimentally. On the other hand, at higher supersaturations where larger aggregates are supported, the chemical system is inherently metastable and therefore likewise challenging to study from an experimental standpoint. Understanding aggregation behavior is further complicated in the case of ionizable drugs where, unlike neutral compounds, there can be uncertainty in the kinds of drug molecules (i.e., charged, neutral, or both) that become incorporated into various clusters, particularly at pH values near the pKa. In this paper, we apply physics-based all-atom molecular dynamics (MD) simulations to study aggregation in the weakly basic drug papaverine and in the weakly acidic drug prostaglandin F2α. We employ in silico tools to construct simulation workflows and comprehensive cluster analysis protocols to elucidate the size distributions and dynamics of the drug aggregates formed at both an experimentally relevant concentration and at high supersaturation. We build on a previously published treatment [Solubility of sparingly soluble ionizable drugs. Adv. Drug Deliv. Rev. 2007, 59, 568-590, DOI: 10.1016/j.addr.2007.05.008] to translate the predicted aggregate distributions of each ionized drug into corresponding pH-solubility curves that can be compared directly to experiment. Our findings show that the assumption of a single predominant (charged) aggregate can be misleading in interpreting experimental pH-solubility curves, as it does not adequately reflect the rich diversity revealed in our simulations. Beyond not accounting for the distribution of ionized drug-containing clusters actually observed in solution, for both drugs we find evidence that neutral drug molecules can also participate in the aggregation phenomena. Notably, we observe that many drug molecules remain as free monomers in solution even under simulated conditions designed to mimic those where there is significant deviation of the experimental pH-solubility curve from the Henderson-Hasselbalch (H-H) equation, often taken to be a clear signpost of drug aggregation.

On the Chemistry of Aqueous Ammonium Acetate Droplets during Native Electrospray Ionization Mass Spectrometry.

Ammonium acetate (NH4Ac) is a widely used solvent additive in native electrospray ionization (ESI) mass spectrometry. NH4Ac can undergo proton transfer to form ammonia and acetic acid (NH4+ + Ac- → NH3 + HAc). The volatility of these products ensures that electrosprayed ions are free of undesired adducts. NH4Ac dissolution in water yields pH 7, providing "physiological" conditions. However, NH4Ac is not a buffer at pH 7 because NH4+ and Ac- are not a conjugate acid/base pair (Konermann, L. J. Am. Soc. Mass Spectrom. 2017, 28, 1827-1835.). In native ESI, it is desirable that analytes experience physiological conditions not only in bulk solution but also while they reside in ESI droplets. Little is known about the internal milieu of NH4Ac-containing ESI droplets. The current work explored the acid/base chemistry of such droplets, starting from a pH 7 analyte solution. We used a two-pronged approach involving evaporation experiments on bulk solutions under ESI-mimicking conditions, as well as molecular dynamics simulations using a newly developed algorithm that allows for proton transfer. Our results reveal that during droplet formation at the tip of the Taylor cone, electrolytically generated protons get neutralized by Ac-, making NH4+ the net charge carriers in the weakly acidic nascent droplets. During the subsequent evaporation, the droplets lose water as well as NH3 and HAc that were generated by proton transfer. NH3 departs more quickly because of its greater volatility, causing the accumulation of HAc. Together with residual Ac-, these HAc molecules form an acetate buffer that stabilizes the average droplet pH at 5.4 ± 0.1, as governed by the Henderson-Hasselbalch equation. The remarkable success of native ESI investigations in the literature implies that this pH drop by ∼1.6 units relative to the initially neutral analyte solution can be tolerated by most biomolecular analytes on the short time scale of the ESI process.

The Two-Digit Rule and Winter’s Formula

No abstract available. Article truncated after 150 words. I recently wondered, “How does the “Two-digit rule” for determining the adequacy of respiratory compensation for metabolic acidosis relate to Winter’s formula?” Many clinicians were taught this rule-of-thumb: the last two digits of the pH (those visible if you hold your thumb over the “7”) should provide an approximation of pCO2 (in mm Hg) in the presence of normal respiratory compensation. Although Winter’s formula is easy to remember and perform, the Two-digit rule is even easier. Winter’s formula and the Two-digit rule have both been derived empirically from clinical data (1,2). But the reason the Two-digit rule should work has never, to our knowledge, been adequately explained. We wondered how the two rules were related. We began with serum HCO3 values ranging from 4 -18 mmol/L and used them to calculate the corresponding predicted pCO2 values using Winter’s formula (3). Next, we used the Henderson-Hasselbalch equation to calculate the corresponding …

Is Your Henderson–Hasselbalch Calculation of Buffer pH Correct?

A survey of 21 free online buffer calculators and apps found only 2 that correctly calculated pH under conditions where [H+] and [OH–] cannot be ignored in the ratio term of the Henderson–Hasselbalch equation. Traditional guidelines for when use of formal concentrations is acceptable were found to be flawed. For acidic (pKa ≤ 7) buffers, the use of formal concentrations is valid when FA–/Ka > 20. For alkaline (pKa ≥ 7) buffers, the approximation is valid when FBH+/Kb > 20. Robust equations for predicting pH of acidic and alkaline buffers are presented, which could be used with programmable calculators and should be used for online buffer calculators and apps.

Prediction of Liquid-Liquid Phase Separation at the Dissolving Drug Salt Particle Surface.

During the dissolution of drug salt particles, liquid-liquid phase separation (LLPS) of a free form can occur within the unstirred water layer (UWL) of the particles (UWL-LLPS). Theoretically, UWL-LLPS occurs when the free form concentration at the salt particle surface (C0) exceeds the intrinsic LLPS concentration (S0LLPS) of the free form. In the present study, we attempted to predict UWL-LLPS based on the intrinsic physicochemical properties of drugs. Cyproheptadine hydrochloride (CPH-HCl), diclofenac sodium (DCF-Na), papaverine hydrochloride (PAP-HCl), and propafenone hydrochloride (PRF-HCl) were selected as model drug salts. The pH0 and C0 values at pHs 4.0-9.5 (citric acid, phosphoric acid, and boric acid, buffer capacity = ca. 4 mM/ΔpH) were calculated using the pKa, solubility product (Ksp), and diffusion coefficient (D) of a drug. S0LLPS was measured using the pH-shift method. UWL-LLPS was predicted to occur when C0 ≥ S0LLPS. The prediction result was then compared with UWL-LLPS observed at each pH by polarized light microscopy (PLM). The pH-LLPS concentration (SpHLLPS) profile of each drug was also measured. UWL-LLPS was approximately correctly predicted for CPH-HCl, DCF-Na, and PRF-HCl. However, UWL-LLPS was not observable when C0 was close to S0LLPS. Furthermore, UWL-LLPS was not accurately predicted in the case of PAP-HCl. The pH-SpHLLPS profile of PAP did not follow the Henderson-Hasselbalch equation, probably because of the formation of cationic aggregates. In conclusion, UWL-LLPS was approximately predictable for drug salts using their intrinsic physicochemical properties (Ksp, pKa, D, and S0LLPS), except for PAP-HCl.

Small Schiff base molecules derived from salicylaldehyde as colorimetric and fluorescent neutral-to-basic pH sensors

The development of pH sensors is very important to distinguish different pHs in several applications. In this study, we examined the change of the side chain moiety on the photophysical properties of eight pH-sensitive small Schiff bases (SBs) that can act as both, colorimetric and fluorometric probes. For that, we synthesized all SBs by condensation between salicylaldehyde with a primary amine (methyl-, ethyl-, isopropyl, propyl-, butyl-, pentyl-, cyclohexyl-, and benzyl-amine). The complete molecular structure was confirmed by 1H NMR, 13C NMR, FTIR, UV–Vis, and by GC–FID purity over 90% was confirmed for all synthesized SBs. Theoretical calculations were also performed to give support to our findings. All synthesized samples were tested as a colorimetric and fluorometric pH sensor in the range of pH 3.0–12.0. All SBs exhibited similar behavior, despite the side chain lengths. The SBs are quite long-lived in water solution, allowing their usage as pH sensor. While between pH 3.0–7.0 they are colorless due to the presence of the protonated species, HSB, above pH 7.0 they turn yellow due to the formation of SB−, indicating that the chromogenic property depends on the pH. Additionally, these SBs also exhibit fluorogenic characteristic as they show fluorescence off at acidic pH 3.0–7.0 and fluorescence on (508 nm) above pH 8.0, exhibiting a linear response between pH 7.0–9.0. The pKa value was calculated using the Henderson–Hasselbalch equation for all SBs, obtaining values from 8.20 to 8.52. All SBs act as pH-sensitive colorimetric and fluorometric probes in neutral-to-basic solutions and this process is reversible.

Strong ions and charge-balance

It has been shown that the ability to predict the pH in any chemically characterized fluid, together with its buffer-capacity and acid content can be based on the requirement of electroneutrality, conservation of mass, and rules of dissociation as provided by physical chemistry. More is not required, and less is not enough. The charge in most biological fluids is dominated by the constant charge on the completely dissociated strong ions but, nonetheless, a persistent narrative in physiology has problematized the notion that these have any role at all in acid-base homeostasis. While skepticism is always to be welcomed, some common arguments against the importance of strong ions are examined and refuted here. We find that the rejection of the importance of strong ions comes with the prize that even very simple systems such as fluids containing nothing else, or solutions of sodium bicarbonate in equilibrium with known tensions of CO2 become incomprehensible. Importantly, there is nothing fundamentally wrong with the Henderson–Hasselbalch equation but the idea that it is sufficient to understand even simple systems is unfounded. What it lacks for a complete description is a statement of charge-balance including strong ions, total buffer concentrations, and water dissociation.

Kinetic modelling of ligand trapping inside acidic vesicles containing alpha-4 beta-2 nicotinic receptors as an explanation for long-term cessation effect of varenicline (Chantix).

Govind's et. al. 2017 paper proposes that the smoking cessation effect of varenicline (or epibatidine) is caused by these molecules being trapped inside acidic vesicles containing α4β2 nicotinic receptors. These ligands are weak bases with high affinity to these receptors. The trapping would lead to their slower release and longer desensitization of the receptors, thereby reducing nicotine upregulation. Meanwhile, nicotine, with lower pKa and lower binding affinity is not trapped within the vesicles. It is unclear whether the acidity of the vesicles and the presence of receptors is sufficient to explain the biphasic trapping behavior observed empirically. To better understand this phenomenon, we model flux of ligands between cellular compartments using Flick's first law of diffusion and the Nernst-Plank Equation. The ratio of neutral to charged ligands within each compartment is calculated via Henderson-Hasselbach equation. Main parameters in the model include the number of vesicles, receptors per vesicle, ratio of vesicles to non-vesicle receptors, pH, membrane permeability, pKa and dissociation constants of the ligand. The system is solved numerically using MATLAB and optimized against empirical data. The results show the experimentally observed biphasic release of epibatidine, affirming the hypothesis of trapping inside the vesicles. Our model also shows that the main trapping effect is due to the presence of receptors inside vesicles, not those located on the cell surface and the high affinity of these ligands to the receptors. The exact acidity level inside the vesicles is not as important. Our model is also able to predict the much faster nicotine outward flow compared with epibatidine. This model can be used to predict the kinetics of other weak basic ligands like those used in positron emission tomography.

Low Serum Bicarbonate in a Patient With Diabetes Mellitus:: A Quiz

Low Serum Bicarbonate in a Patient With Diabetes Mellitus:: A Quiz

Hill-type pH probes.

Sensitive detection of the minute and yet pathologically significant pH variation is important and in fact challenging for the conventional pH probes following the Henderson-Hasselbalch equation, i.e., HH-type probes. A paradigm shift to Hill-type pH probes is ongoing. Bestowed by their positive cooperative acid-base chemistry, their pH-responsive profile follows the Hill equation, which exhibits a narrower acid/base transition width than HH-type probes and warrants a higher detection sensitivity. A polymer-based Hill-type pH-responsive material was first developed. More recently, there emerged several distinct small-molecular approaches to achieve Hill-type pH-responsive profiles. They complement the polymer-based sensing materials in applications where membrane permeability is a concern. In this trends article, we rationalize the molecular origins of their positive cooperativity in pH sensing and highlight some interesting proof-of-concept applications. We also discussed future directions of this dynamic research area.

Acid base disturbances in leptospirosis patients: Comparison of conventional and Stewart method

Background: The Henderson-Hasselbalch equation is used in the conventional assessment of acid-base status. In 1983, P. Stewart put up an alternate strategy. The Henderson-Hasselbalch equation uses variations in PCO2 and bicarbonate to explain the acid-base state. On the other hand, the Stewart theory states that albumin, inorganic phosphate, PCO2, Strong Ion Difference (SID), and SID dictate acid-base status. Therefore, these variables have an important role in clinical management. The metabolic acidosis caused by unmeasured anions is accurately identified by the Stewart physiochemical approach, and it is a predictor of mortality in patients with leptospirosis. Aims and Objectives: Comparison of the leptospirosis patient’s S. albumin (requiring ABG analysis) and arterial blood gas (ABG) analysis parameters (pH, PO2, PCO2, HCO3-, BE, SaO2, S.Na+, S.K+, S.Cl, S.PO43-, and anion gap) to compare the conventional and Stewart methods and determine the type of acid-base disturbances present in leptospirosis patients in the intensive care unit. Materials and Methods: Following approval by the ethics committee, ABG and S. Albumin were taken from the clinical notes of fifty patients. The Henderson-Hasselbalch equation, in its conventional form, was unable to identify complex acid-base problems. Thus, we integrated this with the Stewart method. Results: The majority of leptospirosis patients had a mixed disorder characterized by respiratory alkalosis, metabolic acidosis, and metabolic alkalosis. The most prevalent conditions were metabolic acidosis, respiratory alkalosis, and metabolic alkalosis. Stewart’s method can help explain the cause of metabolic disorders. Stewart’s approach also made occult acid-base disorders visible. Conclusion: Stewart’s approach emphasizes the significance of Na+, K+, Cl-, Alb, and PO43- and clarifies their part in the development of metabolic abnormalities, particularly those involving Alb and PO43-. This demonstrates unequivocally that the cause of the metabolic abnormalities can be explained by Stewart’s method, which is highly helpful in planning the management.

Base (HCO3-/CO32-) Transport Properties of SLC4 Proteins: New Insights in Acid-Base Kidney Physiology.

H+ or base transporters and channels in the mammalian genome play important roles in the maintenance of numerous cellular biochemical and physiologic processes throughout the body. Among the known base transporters, those within the SLC4 and SLC26 gene families are involved in cell, transepithelial, and whole organ function. Whether the functional properties of these transporters involve HCO3-, CO32-, or HCO3-/CO32- stimulated H+ (or OH-) transport has not received widespread attention in the literature. Accordingly, "bicarbonate" is the term typically used in most textbooks without greater specificity. Moreover, clinicians and physiologists have historically focused on the blood HCO3- concentration as the base term in the Henderson-Hasselbalch equation in the analysis of clinical acid-base abnormalities, thus, bicarbonate has been assumed to be the species reabsorbed along the nephron as required to maintain the blood [HCO3-] at approximately 25 mM. However, accumulating data in the literature suggest that carbonate, rather than bicarbonate, is the species absorbed across the proximal tubule basolateral membrane, whereas in the collecting duct, bicarbonate is indeed transported. Various experimental approaches leading to this new concept are herein reviewed.

970: PHYSIOLOGY-BASED VENTILATOR COMPUTER DECISION SUPPORT OUTPERFORMS CLINICIANS IN AN IN SILICO TRIAL

Introduction: Intensivists are routinely required to titrate alveolar minute ventilation based on blood gas information. Survey data show that intensive care trainees feel insufficiently trained in ventilator management. Bedside decision support has the potential to facilitate more efficient ventilator titration and serve as a teaching tool for trainees. Methods: We developed an online ventilator calculator based upon arterial partial pressure of carbon dioxide (PaCO2) and Henderson-Hasselbalch equations, allowing clinicians to input ventilator parameters as well as current and desired blood gas information. We validated predictions among arterial blood gas (ABG) values from a single quaternary academic pediatric intensive care unit (PICU). We included all ABG values obtained between 1/1/2010 and 12/31/2020 among PICU patients receiving invasive pressure control, volume control, or volume targeted ventilation and concurrent pharmacologic muscle relaxation with a repeat blood gas analysis within 1-24 hours. We excluded ABGs from patients on extracorporeal support. We subsequently performed a retrospective in-silico trial on a subset of ABGs meeting criteria for ventilator weaning (pCO2 < 30 and pH > 7.35 or pCO2 < 50 and pH > 7.50) or escalation (pCO2 > 50 and pH < 7.30 or pCO2 > 45 and pH < 7.20), excluding patients with traumatic brain injury. Clinician behavior was compared against calculator recommendations, with a goal of achieving an ABG value that met neither weaning nor escalation criteria. Results: There were 16,835 included ABGs among 664 patients, with a median (IQR) time between ABGs of 3.8 (2.2-4.4) hours. The median (IQR) difference between predicted and actual PaCO2 values was 0.00 (-3.06-3.00) mmHg. 11,460/16,835 (68.1%) PaCO2 values were within 5 mmHg of predicted, and 14,902/16,835 (88.5%) were within 10 mmHg. There were 2,433 ABGs among 350 patients included in the in-silico trial. Calculator recommendations were preferable to clinician behavior in 1,149/1,534 (74.9%) weaning scenarios and 605/899 (67.3%) escalation scenarios. Conclusions: Computer decision support outperformed clinician actions in this retrospective in-silico trial and may provide a useful teaching tool for trainees. Prospective study is needed to determine feasibility and user satisfaction.

Simulations Explain the Swelling Behavior of Hydrogels with Alternating Neutral and Weakly Acidic Blocks

We used computer simulations to study the equilibrium swelling of weak (pH-responsive) polyelectrolyte hydrogels as a function of pH and salt concentration in a supernatant solution. Our simulations were designed to represent recently synthesized gels composed of tetrapoly(acrylic acid) and tetrapoly(ethylene glycol) stars. To model the ionization equilibrium of the weak acid groups and the exchange of small ions with the reservoir, we applied the recently developed grand-reaction Monte Carlo method. We showed that the ionization of these gels as a function of the pH significantly deviates from the ideal Henderson–Hasselbalch equation due to two main contributions: (1) electrostatic interactions and (2) Donnan partitioning of small ions. The first contribution dominates in the gels composed of alternating neutral and acidic blocks, contrasting with our previous observations that both contributions are comparably strong in hydrogels composed of homogeneously distributed weak acid groups. We also critically examined the counterion condensation argument, previously invoked to explain why the experimentally observed swelling was lower than predicted by theory. Thus, a detailed analysis of the simulations allowed us to understand which of the above effects dominates in different systems and why, thereby allowing us to identify the correct physical origin of the deviations from ideal swelling. Such an understanding is important not only for correctly interpreting experimental measurements but also for designing polyelectrolyte gels tailored to exhibit specific swelling response to pH and salt concentration.

LBODP029 Pseudohypobicarbonatemia In The Setting Of Diabetic Ketoacidosis And Severe Hypertriglyceridemia

Abstract Background Severe hypertriglyceridemia is a rare complication of diabetic ketoacidosis (DKA); however, the resulting spuriously low measurements of serum bicarbonate ("pseudohypobicarbonatemia") are less well known. Clinical Case A healthy 15-year-old female presented to the emergency department with polydipsia, polyuria, and abdominal pain. She had a normal BMI and a sibling with type 1 diabetes (T1D). Labs demonstrated serum glucose of 351 mg/dL, serum ketones of 3.4 mmol/L, serum bicarbonate of &amp;lt;5 mmol/L, anion gap of &amp;gt;23 mmol/L, and triglycerides of &amp;gt;21,000 mg/dL. Serum lipase was normal at 70 units/L. She was admitted for protocolized DKA treatment with intravenous fluids and regular insulin drip. Hospital day 2, serum bicarbonate remained very low (7 mmol/L) despite declining ketones (1.9 mmol/L), decreasing anion gap (15 mmol/L), normal chloride (112 mEq/L), and normal lactic acid (1.3 mmol/L). A spurious lab was suspected, so bicarbonate was calculated from a venous blood gas (VBG) which showed a pH of 7.28 and a bicarbonate of 16.2 mmol/L at a time when serum bicarbonate was 7 mmol/L. Serial BMPs and VBGs were trended, with the serum bicarbonate consistently 7-10 mmol/L lower than the blood gas bicarbonate. Her ketoacidosis resolved, yet she remained hospitalized for continued IV regular insulin drip (max 0.3 units/kg/h) for treatment of severe hypertriglyceridemia. On hospital day 7, triglycerides fell below 500mg/dL. She never developed pancreatitis. She was discharged home on multiple daily injection insulin and a low-fat diet. Her triglyceride level two weeks later was 173 mg/dL. Diabetes autoantibodies returned positive, confirming a diagnosis of T1D. Clinical Lessons This case demonstrates that very high triglycerides can occur with pediatric DKA and cause a falsely low serum bicarbonate level, also known as "pseudohypobicarbonatemia". This is due to chemistry panel analyzers using absorbance to estimate bicarbonate levels, which makes them susceptible to triglyceride interference. In contrast, blood gas analyzers use the Henderson-Hasselbalch equation to calculate bicarbonate, thus, are not vulnerable to the same triglyceride interference. This is especially relevant in pediatrics, as triglyceride levels may not be routinely checked for patients in DKA, so massive elevation may be missed. It is also pertinent for centers where serum bicarbonate levels may be trended to monitor for DKA resolution, instead of blood gases. If the serum bicarbonate level remains low in a patient with DKA and resolving ketosis, a blood gas may be obtained as another way of looking at the acid/base status. If there is a discrepancy between the two measurements, triglycerides should be assessed, as this could change management and prevent complications such as pancreatitis. Presentation: No date and time listed

Predicting Experimental B22 Values and the Effects of Histidine Charge States for Monoclonal Antibodies Using Coarse-Grained Molecular Simulations.

Static light scattering (SLS) was used to characterize five monoclonal antibodies (MAbs) as a function of total ionic strength (TIS) at pH values between 5.5 and 7.0. Second osmotic virial coefficient (B22) values were determined experimentally for each MAb as a function of TIS using low protein concentration SLS data. Coarse-grained molecular simulations were performed to predict the B22 values for each MAb at a given pH and TIS. To include the effect of charge fluctuations of titratable residues in the B22 calculations, a statistical approach was introduced in the Monte Carlo algorithm based on the protonation probability based on a given pH value and the Henderson-Hasselbalch equation. The charged residues were allowed to fluctuate individually, based on the sampled microstates and the influence of electrostatic interactions on net protein-protein interactions during the simulations. Compared to static charge simulations, the new approach provided improved results compared to experimental B22 values at pH conditions near the pKa of titratable residues.

Automated pH Adjustment Driven by Robotic Workflows and Active Machine Learning

Buffer solutions have tremendous importance in biological systems and in formulated products. Whilst the pH response upon acid/base addition to a mixture containing a single buffer can be described by the Henderson-Hasselbalch equation, modelling the pH response for multi-buffered poly-protic systems after acid/base addition, a common task in all chemical laboratories and many industrial plants, is a challenge. Combining predictive modelling and experimental pH adjustment, we present an active machine learning (ML)-driven closed-loop optimization strategy for automating small scale batch pH adjustment relevant for complex samples (e.g., formulated products in the chemical industry). Several ML models were compared on a generated dataset of binary-buffered poly-protic systems and it was found that Gaussian processes (GP) served as the best performing models. Moreover, the implementation of transfer learning into the optimization protocol proved to be a successful strategy in making the process even more efficient. Finally, practical usability of the developed algorithm was demonstrated experimentally with a liquid handling robot where the pH of different buffered systems was adjusted, offering a versatile and efficient strategy for a pH adjustment processes.

Understanding the pH Dependence of Supersaturation State—A Case Study of Telmisartan

Creating supersaturating drug delivery systems to overcome the poor aqueous solubility of active ingredients became a frequent choice for formulation scientists. Supersaturation as a solution phenomenon is, however, still challenging to understand, and therefore many recent publications focus on this topic. This work aimed to investigate and better understand the pH dependence of supersaturation of telmisartan (TEL) at a molecular level and find a connection between the physicochemical properties of the active pharmaceutical ingredient (API) and the ability to form supersaturated solutions of the API. Therefore, the main focus of the work was the pH-dependent thermodynamic and kinetic solubility of the model API, TEL. Based on kinetic solubility results, TEL was observed to form a supersaturated solution only in the pH range 3–8. The experimental thermodynamic solubility-pH profile shows a slight deviation from the theoretical Henderson–Hasselbalch curve, which indicates the presence of zwitterionic aggregates in the solution. Based on pKa values and the refined solubility constants and distribution of macrospecies, the pH range where high supersaturation-capacity is observed is the same where the zwitterionic form of TEL is present. The existence of zwitterionic aggregation was confirmed experimentally in the pH range of 3 to 8 by mass spectrometry.

Synthesis, optical and electronic studies of a “clickable” quinoxaline-based pH sensor

A new clickable quinoxaline pH sensor was prepared in three facile steps, and a model clicked product was prepared by a cycloaddition reaction with 1-octyne. The pH dependance of the non-clicked and clicked quinoxalines were studied using absorbance and fluorescence spectroscopy. Both the ground state and excited state pKa’s were determined by fitting the data to the Henderson–Hasselbalch equation. The protonation site was also investigated by correlating chemical shifts in 1H NMR spectra with the addition of acid. The energies of the frontier molecular orbitals, of the four synthesized quinoxalines, were determined using absorbance spectroscopy and cyclic voltammetry. The experimentally obtained values of the frontier molecular orbitals were compared to theoretically obtained values and have good agreement.

α-Cyclodextrin affects the acid-base properties of octanoic acid/sodium octanoate

The interaction of octanoic acid and its conjugate base sodium octanoate with α-cyclodextrin was studied by 1H NMR and isothermal titration calorimetry, respectively, at 298.15 K. The results are in agreement with a 1:1 stoichiometry in the complex. The binding of octanoate with α-cyclodextrin is characterized by a positive entropy, stressing the relevance of hydrophobic interactions. Based on the host-guest complex formation, the effect of α-cyclodextrin on the acidity behavior of the acid was evaluated by potentiometric titration. The results are interpreted in terms of the Henderson-Hasselbalch equation and by using an analytical equation for the titration curve. The apparent ionization constants of the complexes are higher than those obtained in water, indicating that octanoic acid becomes a weaker acid after complexation.